Cincinnati Children’s Research Paves Way For Newly Approved Asthma Drug

Thursday, November 16, 2017

Thanks in part to nearly two decades of research at Cincinnati Children’s Hospital Medical Center, the FDA has approved benralizumab, the first drug designed to specifically deplete eosinophils as a treatment for asthma.

The FDA approved benralizumab as an add-on maintenance treatment for severe asthma with eosinophil involvement. Eosinophils are a type of disease-fighting white blood cell. A higher than normal level of eosinophils can indicate a number of conditions, including infectious diseases and inflammatory disorders.

FDA approval “represents a breakthrough for the field and offers a sigh of relief for the many patients suffering from eosinophilic disorders,” says Marc Rothenberg, MD, PhD, director of Allergy and Immunology and the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s. “While the initial FDA approval of benralizumab is limited to a subset of asthma patients, the treatment holds promise for eosinophilic gastrointestinal conditions, which are commonly treated off-label with asthma-approved drugs.”

Rothenberg began researching eosinophils as a doctoral student at Harvard University in the 1990s. It was at that time that the target of benralizumab (IL-5 and its receptor) were first identified and Rothenberg showed involvement of IL-5 in human disease and its effects on eosinophils.

At Cincinnati Children’s, Rothenberg, along with researchers around the world, provided evidence that eosinophils were pro-inflammatory cells involved in asthma and other allergic diseases. He and his colleagues contributed to the rationale of targeting eosinophils, including performing clinical studies in patients with a variety of eosinophilic disorders.

Rothenberg focuses his lab’s research on elucidating the mechanisms of allergic responses, especially in mucosal tissues such as the gastrointestinal tract and lung. He contributed to research that ultimately resulted in the approval of two drugs that block IL-5 (reslizumab and mepolizumab).

Mepolizumab was the first new asthma drug in more than a decade when it was approved in 2015. These drugs were the first to be approved on the basis of eosinophils mediating disease. They inhibit IL-5, a key eosinophil growth and survival factor. Benralizumab, on the other hand, has a different mechanism of action – directly depleting eosinophils via the IL-5 receptor.

This FDA approval, and its prior approval of reslizumab and mepolizumab, demonstrate that commitment to basic research pays off in the long run, says Rothenberg. This has been a theme of research conducted by Rothenberg and his colleagues at Cincinnati Children’s, who are focused on all aspects of eosinophil-related research, including basic, translational, and clinical interventions, he says.